Browsing by Author "Kumar R."

Now showing 1 - 15 of 15

Amido-amine derivative of alginic acid (AmAA) for enhanced adsorption of Pb(II) from aqueous solution
(Elsevier B.V., 2020) Vaid U.; Mittal S.; Babu J.N.; Kumar R.
The present work reports the alternate synthesis of amido-amine derivative of alginic acid (AmAA) with high degree of functionalization. The AmAA have been characterized for percentage functionalization, functional group change, surface morphology and thermal decomposition behavior. The results indicate that the amido-amine derivatisation of alginic acid (AA) with >95% functionalization, significantly improves its Pb(II) adsorption efficiency (395.72 mg/g to 535.87 mg/g) over the AA. The equilibrium and kinetic studies showed that Langmuir and Freundlich adsorption isotherm models fitted well to the experimental data, and these followed pseudo-second order kinetic model. The FTIR (Fourier transform infrared spectroscopy) and 13C CP-MAS NMR (Cross-polarization magic angle spinning carbon-13 solid state nuclear magnetic resonance spectroscopy) analysis revealed that Pb(II) binds to the carboxyl group in case of AA and to the carbonyl & amine group in case of AmAA, which leads to increase in its adsorption efficiency. The study concludes that the functionalization of amido-amine on AA improves its adsorptive efficiency for Pb(II) from aqueous medium.
Cyclic enaminone as new chemotype for selective cyclooxygenase-2 inhibitory, anti-inflammatory, and analgesic activities
(Elsevier Masson SAS, 2019) Kumar R.; Saha N.; Purohit P.; Garg S.K.; Seth K.; Meena V.S.; Dubey S.; Dave K.; Goyal R.; Sharma S.S.; Banerjee U.C.; Chakraborti A.K.
The cyclic enaminone moiety has been identified as a new scaffold for selective inhibition of cyclooxygenase-2 with anti-inflammatory and analgesic activities. The designed cyclic enaminones have been synthesized conveniently through the development of a new catalyst-free methodology and evaluated for cyclooxygenase (COX-1 and COX-2) inhibitory activities. Three compounds 7d, 8, and 9 predominantly inhibited COX-2 with selectivity index of 74.09, 19.45 and 108.68, respectively, and were assessed for in vivo anti-inflammatory activity in carrageenan induced rat paw edema assay. The anti-inflammatory activity of 7d was comparable to that of celecoxib at a dose of 12.5 mg/kg. However, the compounds 8 and 9 were more/equally effective as anti-inflammatory agent compared to celecoxib at the doses of 12.5 mg/kg and 25 mg/kg and also exhibited anti-inflammatory activity comparable to that of diclofenac. The therapeutic potential of the most active compound 9 was further assessed by performing in vivo thermal and mechanical hyperalgesia tests using various models that revealed its analgesic activity. The in vivo non-ulcerogenicity of 9 revealed the gastrointestinal safety as compared to the non-selective COX inhibitor indomethacin. The in vitro antioxidant activity and in vivo experiments on heart rate and blood pressure provided the cardiovascular safety profile of 9. The molecular docking studies rationalize the COX-2 selectivity of the newly found anti-inflammatory compounds 7d, 8, and 9.
E-pharmacophore guided discovery of pyrazolo[1,5-c]quinazolines as dual inhibitors of topoisomerase-I and histone deacetylase
(Academic Press Inc., 2020) Joshi G.; Kalra S.; Yadav U.P.; Sharma P.; Singh P.K.; Amrutkar S.; Ansari A.J.; Kumar S.; Sharon A.; Sharma S.; Sawant D.M.; Banerjee U.C.; Singh S.; Kumar R.
In the quest to ameliorate the camptothecin (CPT) downsides, we expedite to search for stable non-CPT analogues among 11 motifs of pyrazoloquinazolines reported. E-pharmacophore drug design approach helped filtering out pyrazolo[1,5-c]quinazolines as Topoisomerase I (TopoI) 'interfacial' inhibitors. Three compounds, 3c, 3e, and 3l were shown to be potent non-intercalating inhibitors of TopoI specifically and showed cancer cell-specific cytotoxicity in lung, breast and colon cancer cell lines. The compounds induced cell cycle arrest at S-phase, mitochondrial cell death pathway and modulated oxidative stress in cancer cells. Furthermore, a preliminary study was conducted to explore the feasibility of these compounds to be developed as dual TopoI-HDAC1 (histone deacetylase 1) inhibitors (4a) to combat resistance. Compound 4a was found to possess dual inhibitory capabilities in-vitro. Cytotoxic potential of 4a was found to be significantly higher than parent compound in 2D as well as 3D cancer cell models. Probable binding modes of 4a with TopoI and HDAC1 active sites were examined by molecular modelling.
Effect of 1-allyl-3-methylimidazoleum bromide on the motional dynamics and thermal stability of horse ferrocytochrome c
(American Institute of Physics Inc., 2019) Garg M.; Kumari B.; Kumar R.
The novel green solvent, ionic liquids emerged as potential solvents in executing the various in-vitro protein based applications. In the present study, we investigated the role of 1-allyl-3-methylimidazolium bromide ([Amim]Br) on motional dynamics and thermal stability of ferrocytochrome c (Ferrocyt c) at pH 7.0. Our results revealed that (i) the presence of low concentration of [Amim]Br reduces the levels of thermal motion of the -loop of the native Ferrocyt c (ii) at relatively higher concentrations, the denaturing effect of [Amim]Br increases the thermal motions of the -loop that lead to unfold the proteins, and (iii) [Amim]Br presence in reaction medium decreases the thermal stability of native Ferrocyt c at pH 7.0. � 2019 American Institute of Physics Inc.. All rights reserved.
Geochemical relationship and translocation mechanism of arsenic in rice plants: A case study from health prone south west Punjab, India
(Elsevier B.V., 2020) Sharma S.; Kumar R.; Sahoo P.K.; Mittal S.
Rice is a recognised hyperaccumulator of arsenic (As) and is a serious concern for rice varieties grown in As contaminated soil-water systems. In this regard, groundwater, soil and rice-plant samples (two varieties: PR122 and PUSA1121) collected from 10 sites of district Bathinda were studied for their physicochemical characteristics and As concentration. In vitro studies were carried out to study the role of antioxidant enzymes in As uptake and translocation mechanism. The results showed that the As concentration in water and soil samples ranged from 54 to 132 ?g/L and 6.62–19.56 mg/kg, respectively. The As in rice roots, straw, husk and grains of PR122 ranged from 1.89 to 8.56, 0.20–5.3, 0.12–1.42, 0–0.12 mg/kg, respectively and 1.24–8.16, 0.54–5.11, 0.11–1.06 mg/kg and below detection limit (BDL), respectively for PUSA1121. Although a moderate correlation (r = 0.37) was observed between As in groundwater and soil, the higher As concentration found in both media in Behman and Teona areas indicates that we cannot ignore the role of groundwater in As contamination. Spearman correlation analysis indicates the positive impact of As from groundwater and soil in aerial parts of both rice varieties except grains. In vitro studies showed an increase in antioxidant enzyme activities with the increase in As toxicity (15–60 ?M), which indicates As tolerant behaviour in both rice varieties. The hazard quotient (HQ) for both rice varieties is < 1, which suggest no potential non-cancer health risk, however the cancer risk (CR) for PR122 variety exceeded (2.06 – 10?4) the acceptable limit of 1 × 10?4 (USEPA). Based on the present study, it can be concluded that both the rice varieties are tolerant to As and their grains are safe for human consumption.
Ground/drinking water contaminants and cancer incidence: A case study of rural areas of South West Punjab, India
(Taylor and Francis Inc., 2019) Kaur G.; Kumar R.; Mittal S.; Sahoo P.K.; Vaid U.
This study was carried out in the rural areas of South West Punjab, India, to evaluate the groundwater quality and cancer incidence. The epidemiological study was carried using standardized questionnaire method, and the groundwater samples were analyzed for heavy metals by ICP-MS and AAS. The results showed that the cancer prevalence was highest in the age group of > 60, followed by >45–60 years old in both males and females. The average cancer rate in females (272 cases/lakh) was ?3 times higher than the India's national cancer average of 80 cases/lakh. The mean concentration of As(27.59 µg/L), Pb (48.3 µg/L), U (96.56 µg/L), NO3– (67.32 mg/L), and F– (4.7 mg/L) exceeded the drinking water limits of WHO/BIS. Health risk analysis indicated that As, Pb, U, and F– with NO3– are the major groundwater contaminants, which may be one of the potential cause of cancer incidences. Multivariate analyses reveal that anthropogenic activities are source of NO3–, whereas U, As, and F– are mainly of geogenic origin. The carcinogenic and non-carcinogenic risk followed in the order of As > Pb and U > F–>NO3–>Cu > Zn, respectively. Further, correlations between cancer incidence and groundwater quality have been discussed.
Lysine and ?-Aminoisobutyric Acid Conjugated Bioinspired Polydopamine Surfaces for the Enhanced Antibacterial Performance of the Foley Catheter
(American Chemical Society, 2019) Patel K.; Kushwaha P.; Kumar S.; Kumar R.
Microbial adhesion onto implanted devices was reduced by the immobilization of amino acid lysine and ?-aminoisobutyric acid to polydopamine functionalized PET films and Foley catheters. The polydopamine functionalized film was prepared by a dip coating method followed by incorporation of biocompatible amino acids to prepared films. The purpose of development of the modified pDA film is to improve the anti-biofouling and antibacterial activity of the film which can be successfully applied for medical devices. The characterization of modification was done using different techniques such as contact angle measurement, ATR-FTIR, FE-SEM, AFM, and XPS analysis. ATR-FTIR spectroscopy and XPS confirmed the successful amino modification of film. The anti-biofouling and antimicrobial behavior of the prepared surfaces were evaluated using the bacterial attachment and death assay. The resulting coatings repelled bacterial cell attachment and killed clinically applicable Gram-negative and Gram-positive strains. The developed coatings were applied to the Foley catheters to study the antibacterial activity by the log reduction method. The results demonstrate that tested amino acid-modified film increases the antibacterial activity of the catheters and can significantly help in reduction of nosocomial infections.
Metal- And Solvent-Free Multicomponent Decarboxylative A3-Coupling for the Synthesis of Propargylamines: Experimental, Computational, and Biological Investigations
(American Chemical Society, 2020) Kaur P.; Kumar B.; Gurjar K.K.; Kumar R.; Kumar V.; Kumar R.
Decarboxylative A3-coupling of ortho-hydroxybenzaldehydes, secondary amines, and alkynoic acids is performed under catalyst and solvent-free conditions. The developed methodology provided a waste-free method for the synthesis of hydroxylated propargylamines which are versatile precursors for various bioactive heterocyclic scaffolds. The experimental and density functional theory studies revealed that the in situ-formed ortho-quinonoid intermediate (formed from ortho-hydroxybenzaldehyde and amine) undergoes a concerted Eschweiler-Clarke type decarboxylation with alkynoic acids. The synthesized compounds were evaluated for MAO-A, MAO-B, and AChE inhibitory activities as potential drug candidates for the treatment of various neurological disorders. Compound 4f was found to be the most potent and selective MAO-B (high selectivity over MAO-A) and AChE inhibitor in the series with IC50 values of 4.27 ± 0.07 and 0.79 ± 0.03 ?M, respectively.
Novel 2-(substituted phenyl Imino)-5-benzylidene-4-thiazolidinones as possible non-ulcerogenic tri-action drug candidates: synthesis, characterization, biological evaluation And docking studies
(Birkhauser Boston, 2019) Chawla P.; Kalra S.; Kumar R.; Singh R.; Saraf S.K.
The present research was aimed at the synthesis and screening of 35 novel 2-(substituted phenyl imino)-5-benzylidene-4-thiazolidinones having different substitutions at imino phenyl and arylidene groups. The title compounds were synthesized by Knoevenagel condensation at the 5th position of the 4-thiazolidinone ring, in the presence of sodium acetate. The structures were assigned on the basis of spectral data. The compounds were screened for in vivo anti-inflammatory, antinociceptive and in vitro free-radical scavenging activities. The compounds exhibited significant activities when compared with standard drugs. The distinctive property of the derivatives was that none of them had an acidic group, like conventional NSAIDs, but exhibited significant in vivo activity in acute inflammation models. Further, the active compounds of each series were docked against cyclooxygeanase (COX)-2 enzyme using Glide module of Maestro 11.1 program. It was evident from the docking results that 3-chlorophenylimino and 2-chloro moiety on 5-benzylidene nucleus of the 4-thiazolidinone derivative (30) could easily fit into the COX-2-binding pocket, considered as critical interaction for COX-2 inhibition. Interestingly, some of the compounds exhibited the potential of becoming dual action or even triple action drug candidates, which could target degenerative disorders associated with excessive free-radical generation.
P53-mediated anticancer activity of Citrullus colocynthis extracts
(Bentham Science Publishers, 2019) Joshi G.; Kaur J.; Sharma P.; Kaur G.; Bhandari Y.; Kumar R.; Singh S.
Background: Current anticancer therapeutics comes with significant side effects and thus focus is shifting towards minimizing the side effects or to avoid the disease altogether. Thus, various natural products are being investigated for their potential therapeutic values which can be easily included in daily diet of a person. Citrullus colocynthis (L.) fruit is commonly used in traditional medicines and is known to have antioxidant effects, thus may possess potent anticancer activity as well. Objectives: To establish the anticancer potential of fruit belonging to Citrullus colocynthis (L.) and delineate the potential targets. Results: In the present study it was found that seed and pulp extracts of the fruit are effective against various cancer cell lines while the normal cells, with lower rate of division, remain largely unaffected. The current study for the first time shows that these extracts function via regulation of p53 pathways and the mode of apoptosis is mostly via mitochondrial (intrinsic) pathway. The biological profiling of the extracts was also validated using molecular modelling studies utilizing the two major polyphenols constituents from colocynths i.e., Isoorientin and Isovitexin. Conclusion: The study suggested that the constituent has a multiple target approach for the inhibition of cancer cell proliferation and inhibition of ROS production via the major apoptotic proteins. All of these outcomes suggest and establish a critical role of ROS accumulation and mitochondrial function in the p53-dependent cell.
A panoramic review of IL-6: Structure, pathophysiological roles and inhibitors
(Elsevier Ltd, 2020) Kaur S.; Bansal Y.; Kumar R.; Bansal G.
Interleukin-6 (IL-6) is a pleiotropic pro-inflammatory cytokine. Its deregulation is associated with chronic inflammation, and multifactorial auto-immune disorders. It mediates its biological roles through a hexameric complex composed of IL-6 itself, its receptor IL-6R, and glycoprotein 130 (IL-6/IL-6R/gp130). This complex, in turn, activates different signaling mechanisms (classical and trans-signaling) to execute various biochemical functions. The trans-signaling mechanism activates various pathological routes, like JAK/STAT3, Ras/MAPK, PI3K–PKB/Akt, and regulation of CD4+ T cells and VEGF levels, which cause cancer, multiple sclerosis, rheumatoid arthritis, anemia, inflammatory bowel disease, Crohn's disease, and Alzheimer's disease. Involvement of IL-6 in pathophysiology of these complex diseases makes it an important target for the treatment of these diseases. Though some anti-IL-6 monoclonal antibodies are being used clinically, but their high cost, only parenteral administration, and possibility of immunogenicity have limited their use, and warranted the development of novel small non-peptide molecules as IL-6 inhibitors. In the present report, all molecules reported in literature as IL-6 inhibitors have been classified as IL-6 production, IL-6R, and IL-6 signaling inhibitors. Reports available till date are critically studied to identify important and salient structural features common in these molecules. These analyses would assist medicinal chemists to design novel and potent IL-6 production and signaling inhibitors, through knowledge- and/or computer-based approaches, for the treatment of complex multifactorial diseases.
Recent advancements in mechanistic studies and structure activity relationship of FoF1 ATP synthase inhibitor as antimicrobial agent
(Elsevier Masson SAS, 2019) Narang R.; Kumar R.; Kalra S.; Nayak S.K.; Khatik G.L.; Kumar G.N.; Sudhakar K.; Singh S.K.
The emergence of drug resistance in infectious microbial strains can be overcome by development of novel drug molecules against unexploited microbial target. The success of Bedaquiline in recent years, as FoF1 ATP synthase inhibitor against XDR and MDR mycobacterium strains, has resulted in further exploration to identify more potent and safe drug molecules against resistant strains. FoF1 ATP synthase is the main energy production enzyme in almost all eukaryotes and prokaryotes. Development of bacterial ATP synthase inhibitors is a safe approach, without causing harm to mammalian cells due to structural difference between bacterial and mammalian ATP synthase target sites. This review emphasizes on providing the structural insights for FoF1 ATP synthase of different prokaryotes and will help in the design of new potent antimicrobial agents with better efficacy. Further, applications of synthetic and natural active antimicrobial ATP synthase inhibitors, reported by different research groups are summarized. Their SAR and mode of actions are also analysed. � 2019 Elsevier Masson SAS
Recent advances in decarboxylative C-C bond formation using direct or in situ generated alkenyl acids
(Taylor and Francis Inc., 2019) Kaur P.; Kumar V.; Kumar R.
In recent years, the reactions of abundantly available, inexpensive, and structurally diverse alkenyl acids (-C=C-COOH) with C-X (X = halogen) or C-H coupling partner have emerged as vital strategies for the streamlined synthesis of functionalized alkenes with extrusion of innocuous CO2. Various alkenyl acids such as cinnamic acids can act as stable surrogates for the polymerization prone styrenes/olefins, which otherwise need special attention for their handling and storage. Furthermore, cinnamic acids can be easily prepared through various methodologies including Knoevenagel-Doebner (KD) condensation, Heck coupling reaction, etc. Recently, various one-pot tandem methodologies involving the decarboxylative coupling of KD/Heck sequence with C-H or C-X substrate have come into fore. The present review article edifies about the recent advances, scope and limitations for C-C bond formation via (i) direct decarboxylative functionalization of C-X or C-H substrate with alkenyl acids, (ii) tandem one-pot multicomponent decarboxylative approaches (involving in situ generated alkenyl acids) e.g. coupling of KD/Heck sequences with C-X or C-H substrate.
A review on quinoline derived scaffolds as anti-HIV agents
(Bentham Science Publishers, 2019) Chokkar N.; Kalra S.; Chauhan M.; Kumar R.
After restricting the proliferation of CD4+T cells, Human Immunodeficiency Virus (HIV), infection persists at a very fast rate causing Acquired Immunodeficiency Syndrome (AIDS). This demands the vigorous need of suitable anti-HIV agents, as existing medicines do not provide a complete cure and exhibit drawbacks like toxicities, drug resistance, side-effects, etc. Even the introduction of Highly Active Antiretroviral Therapy (HAART) failed to combat HIV/AIDS completely. The major breakthrough in anti-HIV discovery was marked with the discovery of raltegravir in 2007, the first integrase (IN) inhibitor. Thereafter, the discovery of elvitegravir, a quinolone derivative emerged as the potent HIV-IN inhibitor. Though many more classes of different drugs that act as anti-HIV have been identified, some of which are under clinical trials, but the recent serious focus is still laid on quinoline and its analogues. In this review, we have covered all the quinoline-based derivatives that inhibit various targets and are potential anti-HIV agents in various phases of the drug discovery.
Source apportionment, chemometric pattern recognition and health risk assessment of groundwater from southwestern Punjab, India
(Springer, 2020) Kumar R.; Mittal S.; Sahoo P.K.; Sahoo S.K.
The groundwater quality of southwestern Punjab, India, is a serious cause of concern due to the presence of chemical contaminants in it. However, limited studies of groundwater quality, sources of chemical contaminants and their health risks are available for the region. Hence, this study was conducted to investigate the source, distribution and potential health risk assessment of groundwater quality in three districts of southwestern Punjab, India. The spatial distribution of groundwater chemical contaminants and their potential health risks have been illustrated using inverse distance weighting interpolation technique. The concentration of fluoride (F?; ranged from 0.08 to 4.79 mg L−1) exceeded the WHO limit (1.5 µg L−1) in 80 and 50% samples collected from Bathinda and Ludhiana districts, respectively. The uranium (U) concentration ranged from 0.5 to 432 µg L−1 and shows ~ 85%, 75% and 10% of samples collected from Bathinda, Barnala and Ludhiana districts exceeded the WHO drinking water limit (30 µg L−1), respectively. The groundwater quality of the Bathinda district is a matter of concern due to elevated levels of alkalinity, hardness, fluoride, uranium and nitrate (NO3 ?). The principal component analysis shows close association between F? and U, which indicates their geogenic origin. Further, they also seem to be subordinately influenced by diffuse anthropogenic activities. The clustering of Cu and Pb with NO3 ? and SO4 2? indicates their anthropogenic origin. The non-carcinogenic health risk assessment indicates that F?, NO3 ? and U are the major health risk pollutants in the study area. The carcinogenic health risk of As and Cr exceeded the USEPA limits (10?6) in the entire study area, but observed to be more serious for the district Bathinda (10−3–10−5). The spatial distribution maps illustrate that the health risk for Bathinda district inhabitants is higher than Barnala and Ludhiana districts.